High expression of p300 has an unfavorable impact on survival in resectable esophageal squamous cell carcinoma

Ann Thorac Surg. 2011 May;91(5):1531-8. doi: 10.1016/j.athoracsur.2010.12.012.

Abstract

Background: p300 is a transcriptional regulator that is involved in fundamental processes such as cell proliferation, cell differentiation, and tumor progression. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) has not been elucidated. The purpose of this study was to explore whether there was a correlation between the expression of p300 by immunohistochemistry and the clinical outcome of a group of patients with ESCC treated with surgical resection.

Methods: Tissue microarray that included 240 surgically resected ESCC specimens and 56 cases of paracancerous tissues was successfully generated for immunohistochemical evaluation. The clinical and prognostic significance of p300 expression was analyzed statistically. Kaplan-Meier analysis was used to compare the postoperative survival between groups.

Results: The expression frequency and expression levels of p300 were significantly higher in ESCC specimens (62.5%, 150 of 240) than in normal esophageal mucosa (8.9%, 5 of 56; p<0.001). Increased p300 expression was associated with higher histologic grade (p=0.012), T category (p=0.032), and N category (p=0.013). Patients with low expression of p300 demonstrated higher overall survival compared with those with high expression of p300 (mean, 80.0 months versus 56.9 months; p<0.001). A similar result was observed for disease-free survival (mean, 78.3 months versus 53.1 months; p<0.001). Furthermore, p300 expression could stratify the patient survival (disease-free survival and overall survival) in stage II (p=0.002, 0.003, respectively). Multivariate analysis showed that the level of p300 expression was an independent prognostic factor in ESCC (relative risk, 1.658; p=0.017).

Conclusions: High expression of p300 suggests poor prognosis for patients with resectable ESCC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy, Needle
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / surgery
  • Cohort Studies
  • Disease-Free Survival
  • E1A-Associated p300 Protein / analysis
  • E1A-Associated p300 Protein / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / surgery
  • Esophagectomy / methods
  • Esophagectomy / mortality
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Microarray Analysis
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prognosis
  • Reference Values
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • E1A-Associated p300 Protein
  • EP300 protein, human